The Overview of Dengue Fever

Dengue Fever is a viral disease induced by Dengue virus (of the genus Flavivirus) that is pandemic-prone and is quickly emerging in many parts of the world, most notably in tropical and sub-tropical climates. The disease is created by a mosquito carried viral infection that causes intense flu-like symptoms and can sometimes progress to a potentially fatal stage known as severe dengue. Currently it is estimated that up to 50-100 million infections are estimated annually, spread over more than 100 prone countries, putting at risk close to half of the world's population (World Health Organization, 2018).

The spread of Dengue is due mostly one species of mosquito - Aedes aegypti or 'dengue mosquito', which common appear in tropical locations worldwide. In Australia, towns in North Queensland hold populations of Aedes aegypti and are prone to outbreaks of the virus when the populations are infected by outside sources such as travellers. The species also reside in other locations in central and south Queensland along with the Northern Territory but there have been no recorded outbreaks in recent years. Local mosquitoes remain uninfected unless they have bitten a person who is harbouring the virus. Australia is free of dengue fever except for specific outbreaks, and regimented procedures and vigilant efforts to control the disease are needed to keep it that way (Queensland Health, 2018).

The Causative Agent of the Disease

The Dengue virus (DEN) encompasses 4 main serotypes within the genus Flavivirus, known as DEN-1, DEN-2, DEN-3 and DEN-4. The virus shows a high level of genetic variability, with several distinct genotypes within each serotype having been identified (World Health Organization, 2018).

The structure of the virus is more or less spherical and measures approximately 50nm in diameter. The most important part of the cell is the nucleocapsid, comprised of proteins and the viral genome. Surrounding this is a lipid bi-layer membrane called the viral envelope, taken from the host cell. Still enclosed by the endosome, the virus moves deeper into the cell and is released only when the pH is suitable and the endosome reaches a negative charge. At this stage the nucleocapsid is released into the cytoplasm, where the viral RNA accesses the organelles of the host cell to replicate itself. The virus’ genome within a single strand of positive-sense RNA, which is translated to a single polypeptide and directly broken down into proteins by the host cell’s ribosomes. Three of these are structural proteins, and account for the capsid, membrane and the envelope of the virus. The others are referred to as non-structural proteins and are involved in replication. One in particular, Nonstructural Protein 1 (NS1) has been found to cause adverse effects in the human body through a condition called leaky gut. Once the RNA has been replicated, the newly synthesised genetic material is enclosed in the Rough Endoplasmic Reticulum and matured in the Golgi apparatus, releasing new infectious viral cells into the body to infect more cells (Nature Education, 2014).

Symptoms and Related Issues

Dengue Virus infection can lead to a range of differing clinical symptoms across the spectrum of the disease. This can range from mild fever through to several acute, possibly fatal conditions such as dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue. Age and immunological tolerance both play a role in the severity of the symptoms exhibited. For individuals that develop discernable signs and symptoms, the disease’s course and acuteness can prove difficult to predict in early stages of infection (Queensland Health, 2015).

Classic dengue presents with typical symptoms such as the sudden onset of high fever up to 40 degrees celsius along with consistent headaches and pain at the back of the eyes. Muscle pains are prominent particularly in the back and limbs, as well as joint pain commonly in knees and elbows, and a rash causing skin redness with the presence of small bumps, itchiness and flaking of skin. Other notable symptoms can also be observed, such as lethargy, weakness, loss of appetite leading to weight loss, taste abnormality such as the presence of a displeasing metallic taste. Common flu-like symptoms will persist for days, such as sore throat body pains and coughing, as well as vomiting and diarrhoea.

As the disease develops in the body, abdominal pain may be experienced and minor hemorrhaging such as nosebleeds, abnormally heavy and prolonged periods for women, blood present in urine, and bleeding gums (Australian Government: Department of Health, 2015). Careful monitoring of the infected individual should be undertaken, with hospitalisation possibly being required depending on the severity of signs and symptoms. Such occasions include high level of dehydration, bleeding or the presence of additional co-occurring conditions (such as hepatitis). Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) appear predominantly in the form of plasma leakage, the process in which the proteins and other fluid elements of blood leak from blood vessels into surrounding tissues, causing shock and can be fatal if left untreated (Australian Government: Department of Health, 2015).

Plasma leakage has been observed to occur more often in children and youths and is the most severe complication of the disease spectrum, distinguishing dengue fever from severe dengue (Centers for Disease Control and Prevention, 2019). In general, the illness commonly persits for up to a week, sometimes two, and in some instances symptoms can return for another several days, before alleviating completely (Queensland Health, 2018).

Pathology and Etiology

Dengue Fever’s life cycle involves the mosquito in the role as the transmitter (vector), with humans acting as the main source of infection (victim) (World Health Organization, 2018). In Australia, dengue mosquitoes most commonly live and breed nearby to humans and built up areas, with no large populations being observed in forests or rural areas. These mosquitoes feed throughout the day, predominantly in mornings and evenings. After feeding on the blood of their victims, females lay eggs in water sources like puddles and many artificial places it accumulates such as buckets, containers, clogged roofing gutters and other human-made structures. The eggs eventually hatch into larvae, which develop into adult mosquitoes over 1-2 weeks (Queensland Health, 2018).

The virus is spread to humans via the bites of infected female Aedes aegypti mosquitoes, which is not present in the mosquitoes when born and is most commonly received from the blood of an infected person whilst feeding. Inside the mosquito, it is the gut specifically that harbours the virus and over the course of an 8-12 day incubation period advances to the salivary glands. From here, the virus can be transmitted to humans by the transfer of saliva to body fluid during probing or feeding (World Health Organization, 2018). The time between being infected and becoming infectious is the reason that mosquitoes passing on the virus tend to be the mature females. The mosquitoes will remain infectious for life and can pass on the virus to many new hosts during that time (Queensland Health, 2018).

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Humans will become sick within three to fourteen days after being bitten. The virus circulates through the person’s body via arteries and capillaries for up to seven day, at which time comes the onset of fever. Directly before fever becomes present and up to 12 days following, infected persons can infect new mosquitoes if bitten again, continuing the disease cycle and spread. Dengue fever however does not transmit directly from person to person (World Health Organization, 2018).

Recovery from an infection of the virus in humans results in immunity for life in humans, but this immunity is only for that specific virus serotype. This immunity does however provide partial and short-term protection from the additional three virus serotypes. Evidence has shown that repeated infections have been known to increase the microbial load and put the patient at risk of progressing to severe dengue. It is likely that the time intervals between infections and the sequence of particular serotype infections is also a contributing factor (World Health Organization, 2018).

Due to it’s reliance upon the mosquito as the virus transmitter, Dengue Fever is found in the tropics, where it is widespread. Risk factors pertaining to disease spread are determined by differences in rain patterns, temperature, humidity, degree of urbanisation present and the variables within the urban environment. Until the 1970s, only nine countries had been affected by severe dengue epidemics. Presently, over 100 countries have been categorised by the World Health Organisation (WHO) as being endemic of the disease, encompassing Africa, the Americas, parts of the Medditeranean, South-East Asia and Pacific regions (WHO, 'Dengue Control', 2018). The specific numbers of dengue cases are routinely misclassified and insufficiently reported. One 2013 study estimated 390 Dengue virus infections occur yearly, with only an average of 96 million presenting with clinical indicators of the disease. Although these figures are estimates only, they bring attention to the incredible epidemiological and economic stain that affected countries are presented with (WHO, 'Dengue Control', 2018).

Sample Collection and OHS Measures

Several laboratory testing methods have been implemented to facilitate patient management and disease control. All testing is conducted upon blood sample, which should be provided by the patient as soon as illness is suspected (National Center for Biotechnology Information, U.S. National Library of Medicine, 1970). The purpose of testing, as well as the facilities available and budget considerations will all help to determine the kind of testing method used. The main determinant however is the time of the sample collection relative to the disease process, as this determined if results are viable or not (National Center for Biotechnology Information, U.S. National Library of Medicine, 1970).

The collection and processing of blood and serum create risk of health workers and laboratory staff being exposed to potentially hazardous biological matter. In order to keep the risk of infection to a minimum, safe laboratory techniques must be practised at all times. This includes but is not limited to the use of personal protective equipment and appropriate vessels for sample collection, as well as adherence to standardised handling procedures such as correct refrigeration of samples and sample delivery timelines (National Center for Biotechnology Information, U.S. National Library of Medicine, 1970).

Testing

1. Nucleic Acid Testing. Polymerase chain reaction (PCR) testing has grown in popularity for dengue fever diagnosis due to its ability to yield express results in up to 24hrs, as well as identifying the particular serotype of the infection. This testing method provides a high level of sensitivity of virus detection in the acute phase of the disease period. In order for the tests to be effective viral RNA must be kept intact, therefore samples should be kept refrigerated between 4-8 degrees Celsius during transport and storage. A ‘detected’ dengue PCR test indicates a recent Dengue virus infection, however a ‘non-detected’ reading must be interpreted with the addition of further testing such as antigen detection and serology tests (National Center for Biotechnology Information, U.S. National Library of Medicine, 1970).
2. Antigen detection. Viral antigen detection is a feasible alternative to PCR testing with high sensitivity, and can be used at the beginning of the disease period as early as one day after infection, however the test is unable to detect past infections. The method is highly specific as it tests for the existence of viral antigen non-structural protein 1 (NS1). As this antigen is unique to dengue, detection can differentiate Dengue virus from alternative flavivirus infections. NS1 detection is achieved with enzyme immunoassay via plate assay or lateral flow immunoassays. Antigen detection is useful in conjunction with other testing methods as it does not distinguish between serotypes of the virus (National Center for Biotechnology Information, U.S. National Library of Medicine, 1970).
3. Serology. Enzyme linked immunosorbent assay (ELISA) kits for use with dengue fever are able to give very fast results, but unfortunately these are not specific to the virus in question. A positive result on this test may indicate a recent infection by another flavivirus. ELISA technique is used for detecting Immunoglobulin G (IgG) antibody and is utilsed in confirming recent or former dengue infections in patients showing acute symptoms or those recovering from infection. Because the test is not positive for Dengue virus specifically, the results should be interpreted with caution and while taking into account and context patient report details (National Center for Biotechnology Information, U.S. National Library of Medicine, 1970). Generally speaking, rapid tests tend to lose out on specificity and testing sensitivity while being easy to use and fast acting. High sensitivity and specificity testing is ideal, however more complex technology and higher level of technical aptitude is required for their use (National Center for Biotechnology Information, U.S. National Library of Medicine, 1970).
4. Laboratory diagnosis. Testing human samples for evidence of Dengue virus is completed using commercially available antibody kits. Although these kits have been seen to measure Dengue virus antibodies effectively, they are not specific and will read positive for other flavivirus infections also. These kits are well suited for use in regions that are endemic of the virus or throughout verified epidemics as the likelyihood of the illness being attributed to Dengue virus as opposed to other flavivirus is somewhat high. In locations such as Australia that are not normally affected with Dengue virus with outbreaks less common, the risk of false positive readings is increased, which can unintentionally misguide health authorities and governing bodies. Test results should always be interpreted with care and whenever possible the results should be confirmed by NS1 antigen and/or PCR positivity (Australian Government: Department of Health, 2015).

Treatment

At present, there is no particular dengue fever treatment, and medical care remains largely supportive. Patients should seek medical advice as soon as possible, rest and maintain a high level of fluid intake. Paracetamol may be used to control fever and alleviate joint and muscle pain. Although aspirin and ibuprofen should be avoided as they have the potential to increase the risk of bleeding (Australian Government: Department of Health, 2015).

In the case of severe dengue, emergency medical attention is necessary. Upkeep of the patient’s circulating fluids is achieved with intravenous rehydration and continues to be the primary component of such care, paired with close monitoring in the hospital (NSW Government, 2019).

Reporting and Validation Requirements

Effective disease monitoring depends upon general practitioners, emergency department doctors and laboratories reporting possible cases of dengue to health authorities, especially for people with recent travel history to affected countries (Queensland Health, 2015, p. 27). Under the Public Health Act 2005, it is a mandatory requirement that new cases of Dengue fever even on clinical suspicion, are immediately reported to health authorities in order to prevent the spread of further cases (Queensland Health, 2018).

In areas such as North Queensland, that are home to populations of dengue mosquito, outbreaks prompt intensive control efforts in and around affected premises, with the aim of killing infected females nearby (Australian Government: Department of Health, 2015). The dengue mosquito is known to be highly domestic, and studies suggest that most female dengue mosquitoes maintain a close distance (an average of 400m) to the houses where they emerge as adults (World Health Organization, 2018).

Control measures include indoor spraying with synthetic insecticides such as bifenthrin and deltamethrin. Water collecting vessels and other potential breeding locations are treated with pesticides, insect growth regulators or some species of naturally occurring soil-dwelling bacteria whose spores produce toxins that specifically target mosquito larvae such as Bacillus thuringiensis subspecies israelensis (Bti) (United States Environmental Protection Agency, 2017).